Virulent M. tuberculosis is a facultative intracellular parasite which multiplies freely with the alveolar macrophages of the normal host. The avirulent variant H37Ra is unable to multiply within the normal mouse lung but is progressively eliminated with time. A number of recombinant strains of M. smegmatis and H37Ra have been prepared bearing DNA fragments from virulent H37Ru and tests in intravenously infected mice indicated that same recombinant strains were capable of persisting in the lungs of intravenously infected mice better than controls bearing only plasmid DNA. The in vivo selected recombinant strains will be tested for growth/survival in mouse peritoneal, splenic and alveolar macrophage cultures in tissue culture compared to virulent H37Rv and the parent H37Ra. The macrophages will be infected in vivo and in vitro and the growth compared for macrophages harvested from C57Bl/6 (Bcgs) and A/I (Bcgn) mice. The resulting growth curves will be compared with those observed using J774. Those recombinants which show maximum intracellular growth will be examined for the presence of the 25 kb genomic fragment containing the ivg gene shown earlier to confer an in vivo growth advantage to some recombinant strains of M. tuberculosis.